Substance abuse in pregnancy is known to have deleterious effects
on neonates. These effects differ with respect to the substance ingested
and can include neonatal abstinence syndrome (NAS), low birth weight,
intrauterine fetal demise, and structural abnormalities such as
gastroschisis.

The substance abuse rates have been estimated to be between 2.8-19%
(1,2,3) These reported rates vary based upon the population screened and
the method of screening used.

The lowest number reported in the study by Ebrahim and Gfroerer
utilized a population survey of the entire United States (1) while the
highest rates reported (19%) by Azadi and Dildy utilized urine
toxicology testing. (3) Chasnoff et al developed a screening tool that
estimated that 15% of the population studied continued to use substances
of abuse after becoming aware of the pregnancy. (2)

Recent work published by Montgomery et al compared the performance
of meconium samples versus the testing of umbilical cord tissue. (4)
This study showed concordance of the testing methods that correlated at
or above 90% for all substances analyzed. Follow-up work included a
study in which umbilical cord samples were collected and tested if high
risk criteria for substance abuse were identified. Out of this cohort,
157 of 498 (32%) cords tested positive for substances of abuse. (5)

The number of newborns treated for neonatal abstinence syndrome
(NAS) has increased dramatically in West Virginia. In data collected
from the Cabell Huntington Hospital in Huntington, WV, the number of
neonates treated for NAS increased from 25 in 2003 to 70 in 2007. (6)
The cost difference in the care of an otherwise healthy neonate with NAS
compared to a normal full-term healthy neonate was estimated to be
$3,934 in the Cabell-Huntington cohort. Because of the added costs
associated with the increased risk of prematurity, the average cost of
all infants with NAS was $36,000 compared to $2,000 for a normal
neonate. (6) Obviously any significant reduction in the number of
neonates being treated for NAS can save significant amounts of money for
the healthcare system.

In order to formulate public policy and to ensure that the proper
maternal and neonatal medical services are available in West Virginia to
prevent and to care for pregnancies complicated by substance abuse, an
accurate determination of the rate of substance abuse during pregnancy
as well as the substances involved is required. The objective of our
study was to accurately determine the rate of substance abuse affecting
pregnancy in West Virginia.

Materials and Methods

This study was conceived as an anonymous (no patient information
collected) survey of normally discarded tissue (umbilical cord). As
such, consent was waived and the study was approved by the institutional
review boards at each of the eight participating hospitals. Hospitals
were recruited with the goal having broad geographic distribution and
collection of 1000 samples in one month.

Delivery staff in each hospital was instructed to collect a 6 to 9
inch segment of umbilical cord from as many deliveries as possible for
the month of August (2009). Each sample was stripped of intravascular blood, rinsed in sterile saline, put in a separate sterile plastic
specimen container and frozen for subsequent shipment to United States
Drug Testing Laboratories (USDTL, Des Plaines, IL).

Eight drugs were selected for testing (Table 1). Commercially
available enzyme linked immunoabsorbent (ELISA) kits, with confirmatory
testing by gas chromatography/mass spectometry were used for 6 of the
drugs. Buprenorphine was tested using liquid chromatography/ mass
spectrometry (LCMSMS). Phosphatidylethanol (a metabolite of ethanol)
testing was based on high pressure liquid chromatography/ mass
spectrometry (HPLCMS).

Self reporting was assessed determining the prevalence of drug and
alcohol use reported on birth certificate data as well as a nursing
assessment tool used in West Virginia called the WV Birth Score as
provided by the Office of Maternal Child and Family Health of the State
of West Virginia.

Results

Seven hundred fifty nine (759) samples were collected in one month
and analyzed in batch form by USDTL. The participation by hospital is
shown in Table 2. There were 142 (19.2%) cord specimens positive for
drugs and/or alcohol (Table 3). Polypharmacy was common (Table 4),
especially among those patients using benzodiazapines and methadone.
There was also significant regional variation in drug and alcohol use
(Table 5). Self reporting prevalence rates of drug and alcohol rates are
compared to actual umbilical cord prevalence in Table 6.

Discussion

This anonymous sampling of umbilical cords involving 8 medical
centers in West Virginia identified an overall prevalence of drug and
alcohol use of almost 1 in 5 deliveries. There was a 10-19% prevalence
of substance and 1-15% incidence of alcohol use in patients delivering
during August 2009 with marked underreporting with standard data
collection tools. There was a wide geographic variability in the
prevalence of individual drugs and alcohol with one hospital reporting a
1 in 4 rate of drug and alcohol use! The lack of significant cocaine and
methamphetamine use was surprising. Buprenorphine diversion has also
been noted elsewhere but was not a significant contributor to the drug
problem among these pregnancies.

Some limitations of this study should be noted. The hospitals were
not selected at random. Rather they were selected to optimize the
possibility of obtaining a large enough sample size (approximately 1000
deliveries) to be relevant and where possible to geographically cover
the state of West Virginia. It includes the three tertiary care centers
located in the state which could result in an overestimation of the
prevalence as some out of state referrals may be included. However, the
prevalence of drug exposure at these hospitals was comparable to the
other hospitals in the study. Due to the anonymous nature of the
sampling, it is impossible to analyze reasons for the wide geographic
variations. While factors such as poverty, unemployment, and location of
drug rehabilitation centers may play a role, definitive answers await a
more comprehensive exploration of the problem. Finally, while there are
some well known cross-reactivities on the ELISA screening tests used,
each positive sample was confirmed using gas chromatography/mass
spectroscopy which virtually rules out false positive results.

As noted earlier in the paper, the cost of drug addicted infants
averages $36,000 per infant compared to $2,000 for non-affected infants
(6), with multiple fetal effects contributing to this cost (Table 7).
These findings sparked interest in possible detoxification or
rehabilitation for patients who are using either illegal or
non-prescribed substances or alcohol. The literature previously
described the avoidance of detoxification during the second and third
trimesters of pregnancy due to concerns about harms to the fetus. (7,8)
Recent literature, however, does not substantiate these claims.
(9,10,11) Luty studied 101 opiate dependent women who underwent a 21 day
opiate withdrawal with no adverse effects found. (11) Opioid dependence,
including methadone maintenance, has been linked to fetal death, growth
restriction, pre-term birth, meconium aspiration, and neonatal
abstinence syndrome. (7,12) Neonatal abstinence syndrome may be present
in 60-90% of neonates exposed in-utero with up to 70% of affected
neonates with central nervous system irritability that may progress to
seizures. (13) Up to 50% may experience respiratory issues, feeding
problems, and failure to thrive. (14) These issues are present as well
in those infants whose mothers' are on methadone maintenance. (15)
However, with methadone the onset of neonatal abstinence syndrome may be
delayed for several weeks. (15) Some authors recommend 5-8 days of
maternal hospitalization while their neonates' undergo observation
for neonatal abstinence syndrome. (16) However, most insurance plans
will not reimburse for the prolonged uncomplicated maternal stay.

The incidence of opioid relapse in pregnant opioid abusing women is
very high with 41-96% relapsing. This mirrors the relapse rate of the
general population at 1 month of 65-80%. (17,18) Over 90% of patients
will relapse at 6 months after medication-assisted withdrawal. (19)
Buprenorphine (Subutex[TM]) appears to have no difference in outcomes
with regard to treatment of opiate addicted women. The same neonatal
abstinence syndrome and neonatal effects are present. (20) Treatment of
amphetamine abuse with fluoxetine and imipramine may be useful but is
not a panacea for treatment. A recent review by the Cochrane
Collaboration in 2001 (reissued in 2009) noted that medications are of
limited use in treatment of amphetamine abuse. (21) They note that there
are very limited trials at this time to be able to suggest what is the
best way to treat amphetamine abuse. Benzodiazepine dependence and
detoxification must be done gradually to reduce symptoms. Little has
been written about benzodiazepine detoxification in pregnancy. Alcohol
rehabilitation has had little written and until recently (as found in
our paper) no ability to verify chronic use of alcohol due to its
volatile nature and inability to test for its presence.

Co-morbidities with multiple psychiatric issues in the patients
with substance abuse issues must be considered. Many patients with
substance dependence have affective disorders including: depression,
mania, schizoaffective disorders, schizophrenia, borderline personality,
and bipolar disorders. Therefore, many authors recently note that
detoxification must be linked with a combination of behavioral therapy
with contingency management therapy. (16,22,23) Behavioral therapy
consists of the use of addictions counselors and counseling to assist
substance and alcohol abusers to remain drug and alcohol free. A pilot
program at Charleston Area Medical Center (CAMC) uses this approach with
both individual and group therapy. Contingency management therapies are
a type of psychosocial intervention where the clients receive rewards in
the form of vouchers or prizes if they demonstrate changed behaviors.
There seems to be data to support its use in cocaine and opioid abuse.
(24,25) Due to the large number of patients affected in the State of
West Virginia by both substance abuse and alcohol abuse, we suggest a
programmatic approach with the use of both inpatient and outpatient
therapy be used. Detoxification seems a reasonable approach with
treatment of the psychological co-morbidities associated with substance
use. Multidisciplinary clinics would appear the ideal solution with the
combination of medical, psychiatric, counseling, and social support
necessary to return healthy mothers with healthy drug-free neonates.

Objectives

After completing this program, the reader will be able to quantify
the rate of substance abuse during pregnancy in West Virginia and
describe the maternal, fetal, neonatal and societal consequences of
substance abuse during pregnancy.

References

(1.) Ebrahim SH, Gfroerer J. Pregnancy-related substance use in the
United States during 1996-1998. Obstet Gynecol. 2003;101(2):374-9.

(14.) Cooper JR, Altman F, Brown BS, Czechowicz D. (Eds1983).
Research on the treatment of narcotic addiction: State of the art. (NIDA
Research Monograph 83-1201). Rockville, MD: US Department of Health and
Human Services.

19. Which of the following substances is associated with fetal
growth abnormalities when ingested during pregnancy?

a. Cocaine

b. Marijuana

c. Amphetamines

d. Opiates

e. all the above

20. In the study population, the detection of alcohol ingestion was
similar at all eight of the participating hospitals. True or False?

21. According to the study results, the most frequently abused
substance (excluding tobacco) during pregnancy in West Virginia is:

a. Benzodiazepines

b. Methadone/opiates

c. Alcohol

d. Cannabinoids/marijuana

e. Methamphetamine

Support provided by the West Virginia Department of Health and
Human Resources, Bureau for Public Health, Office of Maternal, Child and
Family Health with federal Maternal and Child Health Block Grant funds.